Cleveland Clinic's Triple-Negative Breast Cancer Vaccine Shows 74% Immune Response Rate in Phase 1 Trial
Key Insights
Cleveland Clinic researchers presented final Phase 1 results for an investigational vaccine targeting triple-negative breast cancer (search), showing a 74% immune response rate across 35 participants.
The vaccine targets α-lactalbumin (search) protein found in 70% of triple-negative breast cancers and was deemed safe with only mild injection site reactions reported.
A Phase 2 efficacy trial is planned for late 2025 to evaluate whether the immune response translates into reduced recurrence risk for this aggressive cancer type.
Cleveland Clinic researchers have presented promising Phase 1 results for an investigational vaccine designed to prevent triple-negative breast cancer (search), the most aggressive form of the disease. The vaccine elicited immune responses in 74% of participants and demonstrated a favorable safety profile, setting the stage for efficacy testing in a planned Phase 2 trial.
Targeting an Aggressive Cancer Type
Triple-negative breast cancer (search) accounts for only 10-15% of all breast cancer (search) cases but causes a disproportionately high number of deaths. The cancer lacks estrogen receptors (search), progesterone receptors (search), and produces little to no HER2 (search) protein, making it resistant to targeted therapies that have transformed treatment for other breast cancer subtypes.
"Triple-negative doesn't have either, so we are left only with chemotherapy," said Dr. Larry Norton, founding medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center. The disease is twice as common in Black women and accounts for 70-80% of breast tumors in patients with BRCA1 (search) gene mutations.
Approximately 40% of women with triple-negative breast cancer (search) experience recurrence within five years of treatment, with about 30% of recurrences occurring in the brain. The cancer can also re-emerge in the lungs, liver, and lymph nodes.
Novel Vaccine Approach
The investigational vaccine targets α-lactalbumin (search), a lactation protein present in about 70% of triple-negative breast cancers but absent in normal aging breast tissue after lactation ceases. The vaccine is designed to train the immune system to produce T-cells that attack and destroy cells expressing this protein.
"The vaccine targets a protein called α-lactalbumin (search), which is present in about 70% of triple-negative breast cancers and found on the surface of tumor cells," according to the research findings. If successful, the vaccine would teach the immune system to recognize and eliminate cancer cells bearing this target.
Phase 1 Trial Results
The Phase 1 study, funded by the U.S. Department of Defense and conducted in partnership with Anixa Biosciences, enrolled 35 patients across three distinct cohorts. The trial evaluated safety and immune response rather than clinical outcomes.
Phase 1a included 26 patients who had completed treatment for early-stage triple-negative breast cancer (search) within three years and were tumor-free but at high risk for recurrence. Phase 1b enrolled four cancer-free individuals with genetic mutations associated with elevated breast cancer (search) risk who elected preventative mastectomy. Phase 1c included five early-stage patients with residual cancer after pre-operative treatment.
"The results from this trial are promising, as they suggest the investigational vaccine is not only safe and well tolerated but also capable of inducing immune responses in over 70% of participants," said Dr. G. Thomas Budd, principal investigator and breast cancer (search) medical oncologist at Cleveland Clinic's Cancer Institute.
Safety Profile and Limitations
The vaccine demonstrated a favorable safety profile with side effects primarily consisting of mild skin inflammation at injection sites. No serious adverse events were reported during the trial.
One important consideration involves potential autoimmune responses. Since women naturally produce α-lactalbumin (search) during lactation, the vaccine could theoretically train the immune system to attack this normal process. "Because of this, Budd said he doesn't recommend that women who want to breastfeed enroll in the trial," according to the research team.
Future Development Plans
While the immune response results are encouraging, researchers emphasize that the clinical significance remains unknown. "Whether this immune response will translate into reducing the risk of recurrence or preventing breast cancer (search), we don't know that yet," Budd acknowledged.
A Phase 2 trial is expected to begin late next year and will be the first to evaluate whether the vaccine can reduce triple-negative breast cancer (search) recurrence risk. This efficacy study is projected to last approximately two to three years. If successful, future trials will test cancer prevention in patients with genetic risk factors.
Scientific Foundation
The vaccine development builds on decades of research by the late Dr. Vincent Tuohy, who held the Mort and Iris November Distinguished Chair in Innovative Breast Cancer (search) Research at Cleveland Clinic. His preclinical work, originally published in Nature Medicine, demonstrated that activating the immune system against α-lactalbumin (search) was safe and effective in preventing breast tumors in mice.
"It was Dr. Tuohy's hope that this vaccine would demonstrate the potential of immunization as a new way to combat breast cancer (search), and that a similar approach could someday be applied to other types of malignancies," said Dr. Justin Johnson, researcher in Cleveland Clinic's Department of Inflammation and Immunity.
Clinical Perspective
Experts view the vaccine approach as particularly promising for prevention rather than treatment of existing cancer. "The most promising use for the vaccine would be to prevent a first cancer occurrence or a recurrence, rather than target lingering cancer cells," said Justin Balko, co-leader of the Breast Cancer (search) Research Program at Vanderbilt-Ingram Cancer Center.
This preference stems from cancer cells' ability to evolve and hide target proteins from immune recognition over time, while new cancer cells are less likely to develop such resistance mechanisms.
The research represents part of a broader effort to identify targetable abnormalities in triple-negative breast cancer (search). "There was a time when we would say HER2 (search) is the worst type of breast cancer (search) you can have, then along came HER2-targeting therapies and now all of the sudden one of the worst prognosis markers becomes one of the best," Norton noted. "This could be the story of triple-negative breast cancer if we find a target for it."